Two Multidrug-Resistant Clinical Isolates of Bacteroides fragilis Carry a Novel Metronidazole ResistancenimGene (nimJ)

Abstract

ABSTRACTTwo multidrug-resistantBacteroides fragilisclinical isolates contain and express a novelnimgene,nimJ, that is not recognized by the “universal”nimprimers and can confer increased resistance to metronidazole when introduced into a susceptible strain on a multicopy plasmid. HMW615, an appendiceal isolate, contains at least two copies ofnimJon its genome, while HMW616, an isolate from a patient with sepsis, contains one genomic copy ofnimJ. B. fragilisNimJ is phylogenetically closer toPrevotella baroniaeNimI andClostridium botulinumNimA than to the other knownBacteroidesNim proteins. The predicted protein structure of NimJ, based on fold recognition analysis, is consistent with the crystal structures derived for known Nim proteins, and specific amino acid residues important for substrate binding in the active site are conserved. This study demonstrates that the “universal”nimprimers will not detect allnimgenes with the ability to confer metronidazole resistance, butnimJalone cannot account for the very high metronidazole MICs of these resistant clinical isolates.